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D C Alexander

Publications and source records attributed to D C Alexander.

At least 19 recordsLinked to original sources
PubMed2004

Diffusion tensor magnetic resonance image regularization.

As multi-dimensional complex data become more common, new regularization schemes tailored to those data are needed. In this paper we present a scheme for regularising diffusion tensor magnetic resonance (DT-MR) data, and more generally multi-dimensional data defined by a direction map and one or several magnitude maps. The scheme is divided in two steps. First, a variational method is proposed to restore direction fields with preservation of discontinuities. Its theoretical aspects are presented, as well as its application to the direction field that defines the main orientation of the diffusion tensors. The second step makes use of an anisotropic diffusion process to regularize the magnitude maps. The main idea is that for a range of data it is possible to use the restored direction as a prior to drive the regularization process in a way that preserves discontinuities and respects the local coherence of the magnitude map. We show that anisotropic diffusion is a convenient framework to implement that idea, and define a regularization process for the magnitude maps from our DT-MR data. Both steps are illustated on synthetic and real diffusion tensor magnetic resonance data.

Algorithms↗
PubMed2002

Detection and modeling of non-Gaussian apparent diffusion coefficient profiles in human brain data.

This work details the observation of non-Gaussian apparent diffusion coefficient (ADC) profiles in multi-direction, diffusion-weighted MR data acquired with easily achievable imaging parameters (b approximately 1000 s/mm(2)). A technique is described for modeling the profile of the ADC over the sphere, which can capture non-Gaussian effects that can occur at, for example, intersections of different tissue types or white matter fiber tracts. When these effects are significant, the common diffusion tensor model is inappropriate, since it is based on the assumption of a simple underlying diffusion process, which can be described by a Gaussian probability density function. A sequence of models of increasing complexity is obtained by truncating the spherical harmonic (SH) expansion of the ADC measurements at several orders. Further, a method is described for selection of the most appropriate of these models, in order to describe the data adequately but without overfitting. The combined procedure is used to classify the profile at each voxel as isotropic, anisotropic Gaussian, or non-Gaussian, each with reference to the underlying probability density function of displacement of water molecules. We use it to show that non-Gaussian profiles arise consistently in various regions of the human brain where complex tissue structure is known to exist, and can be observed in data typical of clinical scanners. The performance of the procedure developed is characterized using synthetic data in order to demonstrate that the observed effects are genuine. This characterization validates the use of our method as an indicator of pathology that affects tissue structure, which will tend to reduce the complexity of the selected model.

Brain↗
PubMed2001

Characterization of the biosynthetic gene cluster for the oligosaccharide antibiotic, Evernimicin, in Micromonospora carbonacea var. africana ATCC39149.

Evernimicin (EV) belongs to the orthosomycin class of antibiotics and consists of several modified L- and D-deoxysugars containing unusual orthoester and glycosyl linkages and two orsellinic acid groups, one that is halogenated. The EV biosynthetic gene cluster from Micromonospora carbonacea var. africana ATCC39149 was localized by hybridization to a dTDP-D-glucose 4,6-dehydratase probe and a 120-kb region containing the EV biosynthetic cluster and surrounding regions has been sequenced. BLAST analysis has identified a type I polyketide synthase for orsellinic acid biosynthesis as well as enzymes required for L- and D-deoxyglucose and D-deoxymannose synthesis. In addition, genes involved in glycosyltransfer and resistance were identified. Insertional mutations in several biosynthetic genes blocked EV production, indicating a role for these genes in EV biosynthesis.

Anti-Bacterial Agents↗
PubMed2001

Does growth retardation indicate suboptimal clinical care in children with chronic renal disease and those undergoing dialysis?

Growth failure is an important problem for children with end-stage renal disease (ESRD). Patients receiving replacement therapy for longstanding renal failure since childhood are likely to report dissatisfaction with certain aspects of their lives, especially with final adult height. Additionally, recent data suggest that growth failure in children with ESRD is associated with adverse clinical outcomes, including more frequent hospitalizations, and increased mortality. Although poor growth is unlikely to be the cause of this increased morbidity, growth failure may be a marker for a group of patients at high risk of adverse events. In this review, the authors describe the prevalence of growth retardation in children in the US with chronic renal disease, and present recent data on morbidity associated with growth failure. After reviewing published reports documenting available strategies to optimize growth, the authors conclude that despite vigilance and aggressive clinical management, a subset of children with long-term renal insufficiency and ESRD may still have poor linear growth. A discussion of "optimal care" leads one to consider evidence of current variability in the management of growth retardation in ESRD, and the strengths and limitations of developing practice guidelines to optimize growth in this population.

Child↗
PubMed2001

Spatial transformations of diffusion tensor magnetic resonance images.

We address the problem of applying spatial transformations (or "image warps") to diffusion tensor magnetic resonance images. The orientational information that these images contain must be handled appropriately when they are transformed spatially during image registration. We present solutions for global transformations of three-dimensional images up to 12-parameter affine complexity and indicate how our methods can be extended for higher order transformations. Several approaches are presented and tested using synthetic data. One method, the preservation of principal direction algorithm, which takes into account shearing, stretching and rigid rotation, is shown to be the most effective. Additional registration experiments are performed on human brain data obtained from a single subject, whose head was imaged in three different orientations within the scanner. All of our methods improve the consistency between registered and target images over naïve warping algorithms.

Adult↗
PubMed2000

Early cephamycin biosynthetic genes are expressed from a polycistronic transcript in Streptomyces clavuligerus.

A polycistronic transcript that is initiated at the lat promoter has been implicated in the expression of the genes involved in early steps of cephamycin C biosynthesis in Streptomyces clavuligerus. pcbC is also expressed as a monocistronic transcript from its own promoter. However, an alternative interpretation involving expression via three separate yet interdependent transcripts has also been proposed. To distinguish between these possibilities, mutants lacking the lat promoter and containing a transcription terminator within the lat gene (Deltalat::tsr/term mutants) were created. This mutation eliminated the production of lysine-epsilon-aminotransferase (the lat gene product) but also affected the expression of downstream genes, indicating an operon arrangement. Production of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) (the pcbAB gene product) was eliminated in Deltalat::tsr/term mutants, while production of isopenicillin N synthase (IPNS) (the pcbC gene product) was greatly reduced. The provision of alpha-aminoadipate to the Deltalat::tsr/term mutants, either via exogenous feeding or via lat gene complementation, did not restore production of ACVS or IPNS. Analysis of RNA isolated from the Deltalat::tsr/term mutants confirmed that the polycistronic transcript was absent but also indicated that monocistronic pcbC transcript levels were greatly decreased. In contrast, Deltalat mutants created by in-frame internal deletion of lat maintained the polycistronic transcript and allowed production of wild-type levels of both ACVS and IPNS.

Cephamycins↗
PubMed1999

A bioactive glass particulate in the treatment of molar furcation invasions.

BACKGROUND: Procedures for the treatment of molar furcation invasion defects range from open flap debridement, apically repositioned flap, hemisection, tunneling or extraction, to regenerative therapies. METHODS: The results of surgical therapy consisting of the clinical parameters of probing depth and bleeding on probing were compared in 15 patients with moderate to advanced adult periodontitis. Each patient received surgical therapy consisting of regenerative therapy using bioactive glass compared to open flap debridement alone in human mandibular molar furcation defects. RESULTS: The results of therapy were statistically significant in the defects treated with the bioactive glass. CONCLUSIONS: This study revealed the benefits of bioactive glass in the treatment of Class II furcation defects regarding the clinical parameters of probing depth reduction and the reduction in bleeding on probing.

Adult↗
PubMed1998

Investigation of the Streptomyces clavuligerus cephamycin C gene cluster and its regulation by the CcaR protein.

As part of a search for transcriptional regulatory genes, sequence analysis of several previously unsequenced gaps in the cephamycin biosynthetic cluster has revealed the presence in Streptomyces clavuligerus of seven genes not previously described. These include genes encoding an apparent penicillin binding protein and a transport or efflux protein, as well as the CmcI and CmcJ proteins, which catalyze late reactions in the cephamycin biosynthetic pathway. In addition, we discovered a gene, designated pcd, which displays significant homology to genes encoding semialdehyde dehydrogenases and may represent the gene encoding the long-sought-after dehydrogenase involved in the conversion of lysine to alpha-aminoadipate. Finally, two genes, sclU and rhsA, with no obvious function in cephamycin biosynthesis may define the end of the cluster. The previously described CcaR protein displays homology to a number of Streptomyces pathway-specific transcriptional activators. The ccaR gene was shown to be essential for the biosynthesis of cephamycin, clavulanic acid, and non-clavulanic acid clavams. Complementation of a deletion mutant lacking ccaR and the adjacent orf11 and blp genes showed that only ccaR was essential for the biosynthesis of cephamycin, clavulanic acid, and clavams and that mutations in orf11 or blp had no discernible effects. The lack of cephamycin production in ccaR mutants was directly attributable to the absence of biosynthetic enzymes responsible for the early and middle steps of the cephamycin biosynthetic pathway. Complementation of the ccaR deletion mutant resulted in the return of these biosynthetic enzymes and the restoration of cephamycin production.

Actinomyces↗
PubMed1997

Clinical use of a bioactive glass particulate in the treatment of human osseous defects.

The dental practitioner has a wide choice of materials available for use in bone grafting procedures. A bioactive glass particulate possesses many favorable qualities not often found in other materials, including the ability to remain where placed even with adjacent suctioning; hemostasis; and incorporation into the host bone without the fibrous encapsulation encountered with most other synthetic materials. It is also quick and easy to prepare. This article reviews clinical experiences with PerioGlas in the setting of private practice periodontics, in which this material was used as the grafting material for periodontal defects, apicoectomies, cysts, and ridge augmentation and maintenance procedures, as well as for implant repairs. Several cases detail the advantages of this grafting material.

Adult↗
PubMed1996

Interleukin-1 beta, prostaglandin E2, and immunoglobulin G subclasses in gingival crevicular fluid in patients undergoing periodontal therapy.

Determination of the presence of inflammatory products found in gingival crevicular fluid (GCF) may be of value in evaluating both periodontal disease status and the outcome of therapy. Immunoglobulin G subclasses 1 through 4 (IgGs), interleukin 1-beta (IL-1 beta), and prostaglandin E2 (PGE2) have all been shown to be present in GCF. This study monitored IgGs, IL-1 beta, and PGE2 in GCF of 18 adult patients as they progressed through periodontal treatment toward maintenance therapy. Sites were selected from the most severely affected sextant as determined by probeable crevice depth (PD) at initial examination (IE). GCF was collected on four occasions: initial examination; 4 weeks after completion of initial therapy (oral hygiene counseling, and scaling and root planing); 3 months after completion of surgery; and 7 to 9 months later at a maintenance visit. All variables were reduced to binary form (positive or negative), and break points chosen to separate the approximately symmetrical bell-shaped areas (negatives) from the skewed tails (positives). Repeated measures analyses of variance were performed to detect significant changes in all variables across time. Significant improvements were observed for all the clinical variables measured: PD, attachment level, and bleeding on probing. However, significant reductions for the GCF components only occurred in the concentrations of IL-1 beta and PGE2, but were not evident until the maintenance sampling. Surprisingly, GCF:serum ratios of IgG subclasses did not change significantly over the course of the investigation. The robustness of the levels of these components may be due to inflammation associated with the healing process, or to a further plaque induced response.

Adult↗
PubMed1996

Immunomodulatory and superantigen activities of bacteria associated with adult periodontitis.

Immune dysfunctions are frequently associated with chronic inflammatory diseases. Several investigators have reported that patients with severe periodontitis show reduced or negligible levels of proliferative responses of peripheral blood and gingival lymphocytes to periodontopathic organisms. The purpose of this study was to evaluate the influences of products from Porphyromonas gingivalis (P. gingivalis) and Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) on lymphocytes obtained from periodontally diseased and non-diseased individuals in order to extend our understanding of the possible role of such bacterial components as immune modulators. Pooled cultures of either P. gingivalis or A. actinomycetemcomitans were disrupted using glass beads in a bead mill to prepare whole cell homogenates. These homogenates were then co-cultured with human peripheral blood mononuclear cells (PBMC) and known lymphocyte stimulators. Cultures were pulsed with tritiated thymidine, harvested, and radio label incorporation was determined. Responses to toxic shock syndrome toxin-1 (TSST-1) and pokeweed mitogen (PWM) were inhibited at high concentrations of bacterial homogenate. However, as the concentration was reduced, responses induced by PWM were restored while TSST-1 induced responses remained inhibited. Such results suggest that P. gingivalis and A. actinomycetemcomitans contain potent immunosuppressants with differential influences on lymphocyte population. These effects on B- and T-cells are independent of periodontal disease status and appear to exert their influence through non-toxic mechanisms. In addition, work currently underway presently indicates that obligate oral anaerobic bacteria such as P. gingivalis produce substances with some of the characteristics of superantigens.

Adult↗
PubMed1996

The evaluation of a managed dental delivery concept.

Phased dentistry (PD) is a philosophy of managed oral health care that emphasizes an orderly approach to dental risk assessment, prevention, and disease management. PD is divided into two stages. Phase I (PH1) care is intended to eliminate all conditions that may produce a dental emergency within 12 months. PH1 care is directed primarily to recruits and apprentice training students. Phase 2 (PH2) care strives to attain and maintain optimal oral health for Navy and Marine Corps personnel after their initial training period and throughout their military career. The purpose of this study was to evaluate the feasibility of introducing PH1 into a recruit dental treatment facility. Data were obtained at Naval Dental Center (NDC), Orlando from 4,571 recruit dental patients who were in-processed and completed recruit training between May 27 and October 1, 1993. The incoming operational dental readiness (ODR) of recruits during the PD trial was 28.5%, whereas the ODR of graduating recruits was 85.8%. During this same period there was a 34% increase in completed dental treatments per provider full time equivalent. Although dramatic increases in ODR and productivity were noticed during PD, other variables may have contributed to these results.

Dentistry↗
PubMed1996

Dental recall status and unscheduled dental attendances in British warships.

When deployed away from base, men and women aboard seagoing vessels have restricted access to dental care. Situations may arise in which untreated disease, acute infections, failing restorations, or trauma result in pain or discomfort. Military dental health care delivery systems seek to minimize episodes of dental pain through routine screening by recall and delivery of treatment. A 12-month survey of all unscheduled attendances aboard British warships was conducted to establish the frequency and nature of cases, particularly with respect to recall status. One thousand three hundred forty-one reports were received from 66 ships and shore-based clinics, equivalent to approximately 52 occurrences per 1,000 personnel per year. The nature of the causes was widely varied. Significant relationships were apparent for recall status (treatment required) and the reported causes of dental caries (odds ratio [OR] 4.16, 95% confidence interval [CI] 1.34-13.8), periapical abscess (OR 3.19, CI 1.06-10.03), and failed restorations (OR 4.22, CI 1.31-15.01). In terms of mean time elapsed since last dental visit, those cases in the Fit/Fleet Ready group went 154 days, whereas those in the Treatment Required dental recall group went a mean of only 95 days.

Adult↗
PubMed1995

The subcutaneous array: a new lead adjunct for the transvenous ICD to lower defibrillation thresholds.

Despite the benefits of transvenous implantable cardioverter defibrillators (ICDs), concern exists that patients with high defibrillation thresholds (DFTs) have an inadequate safety margin between the DFT and the maximum defibrillator energy. A new transvenous ICD lead adjunct, a subcutaneous lead array (SQ Array), was developed to increase safety margins by lowering DFTs. Composed of three lead elements joined in a common yoke, the SQ Array is tunneled subcutaneously in the left lateral chest. Serving as their own controls, 20 patients were studied intraoperatively comparing transvenous lead-alone DFTs with lead-SQ Array DFTs. Seventeen males and three females were randomized to receive the SQ Array through the CPI Ventak PRx/Endotak 70 series protocol. Mean patient age was 63.7 +/- 2.5 years and mean ejection fraction 0.34 +/- 0.04. DFTs were determine using a precise protocol of step-down/step-up testing commencing at 20 joules. Lead-alone DFTs were tested using the proximal coil as the anode (+). For the lead-SQ Array, the proximal coil and the array were linked as a common anode. The lead-SQ Array resulted in a statistically significant reduction in mean monophasic DFT from 23.3 +/- 2.3 joules (lead-alone) to 13.5 +/- 1.9 joules (lead-SQ Array) (P < 0.001). Six patients had lead-alone DFTs > 25 joules but did not require thoracotomy because of adequate DFT reduction with the SQ Array. We conclude that the SQ Array adjunct to the transvenous ICD lead lowers monophasic DFTs an average of 9.8 joules (40.6%) obviating the need for a thoracotomy in selected patients.

Adult↗
PubMed1994

Cloning, sequencing and disruption of a gene from Streptomyces clavuligerus involved in clavulanic acid biosynthesis.

During the purification of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) from Streptomyces clavuligerus, a small protein (CLA) involved in clavulanic acid production co-purified with ACVS. A 24-mer mixed-DNA probe based on the N-terminal amino-acid sequence of CLA was used to isolate the corresponding gene (cla), located near one end of the known cluster of penicillin and cephamycin biosynthetic genes, 5.7 kb downstream from the pcbC gene which encodes isopenicillin-N synthase. The sequence of cla would encode a protein of 313 aa with a high degree of similarity to amidinohydrolase enzymes. The cla gene is located immediately upstream from the previously described clavaminate synthase 2-encoding gene (cs2), and cla homologs were only present in streptomycetes which produced clavam compounds. Replacement of cla with a disrupted copy of the gene blocked the production of clavulanic acid in starch asparagine medium (SA).

Amino Acid Sequence↗
PubMed1994

Role of the rfe gene in the biosynthesis of the Escherichia coli O7-specific lipopolysaccharide and other O-specific polysaccharides containing N-acetylglucosamine.

We report that rfe mutants of wild-type strains of Escherichia coli O7, O18, O75, and O111 did not express O-specific polysaccharide unless the rfe mutation was complemented by a cloned rfe gene supplied in a plasmid. The O polysaccharides in these strains are known to have N-acetylglucosamine (GlcNAc) in their O repeats. In addition, in vitro transferase assays with bacterial membranes from either the O7 wild-type strain or its isogenic rfe mutant showed that GlcNAc is the first carbohydrate added onto the lipid acceptor in the assembly of the O7 repeat and that this function is inhibited by tunicamycin. Our results indicate that the rfe gene product is a general requirement for the synthesis of O polysaccharides containing GlcNAc.

Acetylglucosamine↗